Large (>3.8 cm) Clear Cell Renal Cell Carcinomas are Morphologically and Immunohistochemically Heterogeneous

L. Zaldumbide, A. Erramuzpe, R. Guarch, J.M. Cortes and J.I. Lopez. Large (>3.8 cm) Clear Cell Renal Cell Carcinomas are Morphologically and Immunohistochemically Heterogeneous. Virchows Archives 466:61-66, 2015 [pdf]

Heterogeneity is an inherent event to tumor development that is lately receiving much attention in oncologic research. The topic is being addressed primarily at the molecular level and results are promising. However, translation to practical medicine is still pending. Our intention in this study is to approach the problem in a series of clear cell renal cell carcinomas with the tools that pathologists use in routine practice. Three randomly selected areas of 48 clear cell renal cell carcinomas prospectively collected in two different institutions were analyzed for intratumor heterogeneity. Evaluated parameters were: tumor size, cell type (clear vs. eosinophilic), Fuhrman grade, and immunohistochemical expression of carbonic anhydrase 9, BAP-1, COX-2 and Ki-67. Intratumor heterogeneity was detected in 26 cases (54%). Cell type, grade and Ki67 index were the parameters more frequently heterogeneous amounting respectively 44%, 42% and 38%. Tumor size was a significantly discriminative factor to predict tumor heterogeneity, with a cut-off of 3.8 cm (p<0.001). Aside from tumor size, the most relevant parameters related with intratumor heterogeneity were cell type (clear vs eosinophilic), Fuhrman grade, and Ki67 and COX-2 expression patterns. Carbonic anhydrase 9 and BAP-1 did not show statistical relevance. We conclude that heterogeneity is a common event in clear cell renal cell carcinomas that may be overlooked in cases insufficiently sampled. Tumor size appears as a reliable tool in identifying this situation since clear cell renal cell carcinomas under 3.8 cm in diameter are always homogeneous. This point may help the pathologist to make decisions in tumor sampling.

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